4-Methylmorpholine → (R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate

HRID 59905노트

반응식

HRID 59905 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7]([O:9][CH3:10])=[O:8].CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH2:43]([O:45][C:46]1[CH:67]=[CH:66][CH:65]=[CH:64][C:47]=1[O:48][C@@H:49]1[CH2:54][CH2:53][CH2:52][N:51]([C:55]2[N:60]=[CH:59][C:58]([C:61](O)=[O:62])=[CH:57][N:56]=2)[CH2:50]1)[CH3:44]>C1COCC1.CS(C)=O>[CH2:43]([O:45][C:46]1[CH:67]=[CH:66][CH:65]=[CH:64][C:47]=1[O:48][C@@H:49]1[CH2:54][CH2:53][CH2:52][N:51]([C:55]2[N:60]=[CH:59][C:58]([C:61]([NH:2][CH2:3][C:4]3[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=3)[C:7]([O:9][CH3:10])=[O:8])=[O:62])=[CH:57][N:56]=2)[CH2:50]1)[CH3:44]

참가 물질

8

반응물 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2794825Methyl 3-(aminomethyl)benzoate HydrochlorideHCID 118366221(R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid

생성물 1

HCID 118366276(R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate수율 74.5%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8028Tetrahydrofuran용매

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온도
15 °C

실험 절차

To a 500-mL 3-neck flask was added methyl 3-(aminomethyl)benzoate hydrochloride (12.9 g, 64.1 mmol) followed by DMSO (26 mL). The solution was cooled to 15° C. N-Methyl morpholine (27 mL, 240 mmol) was added followed by EDCl (13 g, 68 mmol) and HOBT (4.09 g, 30 mmol), maintaining the temperature at 15° C. A solution of (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid (20.94 g, 60.98 mmol) in THF (100 mL) was added dropwise over 10 min. The reaction mixture was warmed to 20-25° C. and stirred for 4 hours. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL). The aqueous phase was further extracted with ethyl acetate (2 times with 100 mL). The combined organic extracts were rinsed sequentially with water (200 mL), saturated aqueous sodium bicarbonate solution (2 times with 100 mL), and brine (2 times with 25 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated to afford (R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate (22.3 g). MS (ES+) 491.3 (M+H).

후처리

  1. temperaturemaintaining the temperature at 15° C
  2. temperatureThe reaction mixture was warmed to 20-25° C.
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL)
  5. extractionThe aqueous phase was further extracted with ethyl acetate (2 times with 100 mL)
  6. washThe combined organic extracts were rinsed sequentially with water (200 mL), saturated aqueous sodium bicarbonate solution (2 times with 100 mL), and brine (2 times with 25 mL)
  7. dry with materialThe organic layer was then dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-3980f80b95d54813af43c984dd55e2ae
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440949B2

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